Patients with schizophrenia exhibit behavioral and physiological impairments in the perception, modulation[unreadable] and evaluation of environmental stimuli. These information-processing deficits disrupt patients' efforts to[unreadable] detect, interpret and assign salience to incoming stimuli, resulting in disturbed behavioral responses.[unreadable] Clinically, this can result in hallucinations, ideas of reference, impaired affective expression and abnormal[unreadable] social interactions. Although memory deficits are among the most obvious and pervasive cognitive[unreadable] mpairments in schizophrenia, there is a growing body of evidence that very early elements of information[unreadable] processing, including perceptual integration and deviance detection, are also disrupted. Results of previous[unreadable] CCNMD event-related potential (ERP) studies demonstrated that: 1) deficits in early sensory processes[unreadable] contribute substantially to the deficits observed in later cognitive operations; 2) early sensory deficits are[unreadable] evident in both the auditory and visual sensory systems; 3) early sensory deficits are indicators of genetic[unreadable] vulnerability to schizophrenia. Animal and post-mortem studies suggested that genetically-mediated[unreadable] disturbances in glutamatergic transmission and synaptic function contribute to these ERP abnormalities.[unreadable] The current proposal will build upon these initial findings by further delineating the nature and etiology of[unreadable] deficits in early stimulus encoding and deviance detection. Patients, unaffected family members and healthy[unreadable] controls (80 subjects / group) will be studied using experimental protocols and analytic methods designed to[unreadable] assess the contributions of gamma and theta oscillations to these sensory processing disturbances. Evoked[unreadable] and induced gamma and theta rhythms constitute fundamental mechanisms for feature recognition and[unreadable] context-sensitive processing of sensory information, and are mediated by synaptic activity in the neural[unreadable] structures and transmitter systems implicated in schizophrenia. To determine the contribution of specific[unreadable] genetic vulnerability factors to these neural abnormalities, subjects will be categorized with respect to highrisk[unreadable] haplotypes for three genes that have been implicated in schizophrenia and that modulate pre- or postsynaptic[unreadable] glutamatergic neurotransmission or intracellular signaling: dysbindin (DTNBP1), neuregulin (NRG1)[unreadable] and RGS4. These studies will increase understanding of the brain abnormalities that underlie the cognitive[unreadable] impairments of schizophrenia. This, in turn, could provide the basis for developing new types of treatments.